Incidence of new-onset hypertension before, during, and after the COVID-19 pandemic: a 7-year longitudinal cohort study in a large population.

BACKGROUND: While the augmented incidence of diabetes after COVID-19 has been widely confirmed, controversial results are available on the risk of developing hypertension during the COVID-19 pandemic. METHODS: We designed a longitudinal cohort study to analyze a closed cohort followed up over a 7-year period, i.e., 3 years before and 3 years during the COVID-19 pandemic, and during 2023, when the pandemic was declared to be over. We analyzed medical records of more than 200,000 adults obtained from a cooperative of primary physicians from January 1, 2017, to December 31, 2023. The main outcome was the new diagnosis of hypertension. RESULTS: We evaluated 202,163 individuals in the pre-pandemic years and 190,743 in the pandemic years, totaling 206,857 when including 2023 data. The incidence rate of new hypertension was 2.11 (95% C.I. 2.08-2.15) per 100 person-years in the years 2017-2019, increasing to 5.20 (95% C.I. 5.14-5.26) in the period 2020-2022 (RR = 2.46), and to 6.76 (95% C.I. 6.64-6.88) in 2023. The marked difference in trends between the first and the two successive observation periods was substantiated by the fitted regression lines of two Poisson models conducted on the monthly log-incidence of hypertension. CONCLUSIONS: We detected a significant increase in new-onset hypertension during the COVID-19 pandemic, which at the end of the observation period affected ~ 20% of the studied cohort, a percentage higher than the diagnosis of COVID-19 infection within the same time frame. This observation suggests that increased attention to hypertension screening should not be limited to individuals who are aware of having contracted the infection but should be extended to the entire population.

Achieving a Systolic Blood Pressure Below 130 mmHg Reduces the Incidence of Cardiovascular Events in Hypertensive Patients with Echocardiographic Left Ventricular Hypertrophy.

Background: Recent reports have evidenced an increased mortality rate in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) achieving systolic blood pressure (SBP) <130mmHg. However, to the best of our knowledge, the actual effects of BP reduction to the {less than or equal to}130/80mmHg target on the incidence of cardiovascular events in hypertensive patients with a diagnosis of LVH based on echocardiographic-criteria (Echo-LVH) have never been determined. Methods: In order to fill this long-standing knowledge gap, we harnessed a population of 9511 hypertensive patients, followed-up for 33.6 [IQR 7.9-72.7] months. The population was divided into six groups according to the average SBP achieved during the follow-up ({less than or equal to}130, 130-to-139, and {greater than or equal to}140mmHg) and absence/presence of Echo-LVH. The primary endpoint was a composite of fatal or non-fatal myocardial infarction and stroke, sudden cardiac death, heart failure requiring hospitalization, revascularization, and carotid stenting. Secondary endpoints included atrial fibrillation and transient ischemic attack. Results: During the follow-up, achieved SBP and diastolic BP (DBP) were comparable between patients with and without Echo-LVH. Strikingly, the rate of primary and secondary endpoints was significantly higher in patients with Echo-LVH and SBP>130mmHg, reaching the highest rate in the Echo-LVH group with SBP{greater than or equal to}140mmHg. By separate Cox multivariable regressions, after adjusting for potential confounders, both primary and secondary endpoints were significantly associated with SBP{greater than or equal to}140mmHg and Echo-LVH. Instead, DBP reduction {less than or equal to}80mmHg was associated with a significant increased rate of secondary events. Conclusions: In hypertensive patients with Echo-LVH, achieving an average in-treatment SBP target {less than or equal to}130mmHg has a beneficial prognostic impact on incidence of cardiovascular events. Significance Statement In contrast with recent reports, achieving in-treatment SBP≤130mmHg reduces the incidence of CV events in hypertensive patients with Echo-LVH. Reducing DBP≤80mmHg is instead associated with a higher rate of CV complications. By Cox multivariable regression models, adjusting for potential confounders, the rate of hard and soft CV events was significantly associated with Echo-LVH and SBP≥140mmHg. Our data indicate that therapeutic strategies in patients with Echo-LVH should aim at reducing SBP≤130mmHg paying attention to not reducing DBP≤80mmHg.

Adherence to Mediterranean diet among patients with acute cardiovascular events admitted in Cardiac Rehabilitation unit.

The Mediterranean Diet plays a critical role in the prevention of primary cardiovascular disease (CVD). Actually, there is a scarcity of evidence for secondary prevention. The current study aims to assess adherence to the Mediterranean diet (MD) in patients recently admitted to the Cardiac Rehabilitation Unit following acute cardiovascular disease. Adherence to MD was assessed in 111 patients admitted to the Cardiac Rehabilitation Unit of the Federico II Hospital in Naples. The Medi-Lite score was used to assess adherence to MD. The main determinant of reduced MD compliance was assessed using Pearson's correlation analysis and a multivariable regression model. The population had a median MD adherence score of 11 and a mean score of 10.9. The lowest possible score was 5 (indicating poor adherence), and the highest possible score was 15 (excellent adherence index). There were 3 participants with a poor score (<7), 82 with a good score (7-12), and 26 with an excellent score (³13). Lower Medi-Lite score was associated with younger age and being an active worker in a multivariate regression model (both p<0.05). Our findings show that among patients admitted to the Cardiac Rehabilitation Unit after a major CV event, young active workers have the lowest adherence to MD, requiring an individualized and multidisciplinary approach to improve their adherence to MD for secondary CV prevention.

"Medical Assistance in Contextual Awareness" (AMICO): A Project for a Better Quality of Care for Patients in Cardiac Rehabilitation Unit.

The "Medical Assistance in Contextual Awareness" (AMICO) project proposes an infrastructure, called an "instrumented environment", consisting of the home environment and the person, both of which are suitably equipped with sensors, a telemedicine service platform (in the Internet of Things) and a Robot who acts as a mediator/master between the person, the surrounding environment and the external environment. This infrastructure, oriented to the citizen's well-being, can offer both services oriented to the person in his home environment, monitoring their behavior and psycho-physical state, and telemedicine services to support the remote monitoring of citizens affected by a cardiovascular event undergoing rehabilitation therapies from part of doctors or caregiver.

Lung ultrasound: a narrative review and proposed protocol for patients admitted to Cardiac Rehabilitation Unit.

Lung ultrasonography (LUS) has become in the last 10 years a technique that has reduced the need of second level diagnostic methods such as chest X-ray (CXR) and computerize tomography (CT) for the diagnostic imaging of lung and pleural space, throughout its diagnostic accuracy, radiation free, low cost, real time and bedside approach. The common use of LUS has been recently extend to cardiac and pulmonary disease even in context of Cardiac Rehabilitation Unit and it could be an additional tool for physiotherapist for the management of patients during Rehabilitation course. The authors performed a literature review in PubMed and suggested a new standardize protocol for LUS, based on guidelines and expert consensus document, for patients admitted to Cardiac Rehabilitation Unit. In this protocol, LUS should be performed in six scan each hemithorax, covering twelve imagine regions. For each scan will be noted a specific physiologic or pathological patterns. Furthermore, we suggest for each patient, the use of the Lung Ultrasound Score (LUS score) to obtain a global view of lung aeration and to monitor any changes during the hospitalization. An increase in score range indicates a more severe condition. This Lung Ultrasonography Protocol should be performed in all patients at the time of admission to Cardiac Rehabilitation Unit to monitoring the aeration of the lungs and the possible lung and/or pleura complications after a cardiac disease avoiding the use of second level surveys.

Low Awareness of Cardiovascular Risk Factor Among Patients Admitted in Cardiac Rehabilitation Unit.

INTRODUCTION: Cardiovascular diseases (CVD) are still the leading cause of death and disability worldwide despite the availability of well-established and effective preventive strategies. AIM: We aim to assess patients awareness of the main modifiable cardiovascular risk factors in a population with recent acute coronary syndrome (ACS) admitted in cardiac rehabilitation unit. METHODS: 50 patients with recent ACS have been recruited. We used a 9-items questionnaire about awareness of CV risk factors and eating habits. RESULTS: Many patients underestimate the role of physical activity (PA), cigarette smoking and diabetes as main CV risk factors. Although the importance of good eating habits as cardiovascular protector is well known, only few participants declare a healthy balanced diet. CONCLUSIONS: This study revealed low awareness of common CV risk factors among patients with recent ACS. Individual training plans and the use of technological development to improve awareness and adherence are needed especially in high risk population.

Assessment of carotid cross-sectional area in hypertensive patients: phenotyping and prognostic validation in The Campania Salute Network.

Increased intima-media thickness (IMT) of common carotid artery (CA) is considered the hallmark of vascular hypertension-mediated target organ damage, even if vessel remodeling due to mechanical stress may also induce changes in diameter. We developed a method computing both diameter and IMT of CA, to assess correlates and prognostic impact of carotid cross-sectional area (CCSA) in a large registry of treated hypertensive patients. We selected 6300 hypertensive patients of the Campania Salute Network registry free of overt cardiovascular (CV) disease and with available CA ultrasound (54 ± 11 years; 57% male). CCSA was computed as:[Formula: see text]CCSA was considered high if >90th percentile of the sex-specific distribution (>48 mm2 in men and >41 mm2 in women). Patients with high CCSA were male, with older age, higher pulse pressure (PP), more prevalent obese and diabetic, with higher total and LDL cholesterol (p < 0.01 for all). During a median follow-up of 60 months (IQR 19-87), 206 incident composite major and minor CV events occurred. In Cox regression analysis high CCSA was associated with more than 100% increased risk of incident CV events ((HR 2.11, 95%CI 1.46-3.1, p < 0.0001), independently of the effect of older age, male sex, PP > 60 mmHg, presence of left ventricular hypertrophy (LVH), carotid plaque (CP), and less anti-RAS therapy (p < 0.05 for all). In treated hypertensive patients, increased CCSA is associated with worse metabolic and lipid profile and predict incident CV events, independently of high PP, presence of LVH and CP.

Serum Uric Acid and Left Ventricular Mass in Essential Hypertension.

Serum uric acid (sUA) has been associated with cardiovascular risk. Although the recent mechanistic hypothesis poses the basis for the association between sUA and left ventricular mass index (LVMi), the issue remains poorly investigated in a clinical setup. Through a retrospective analysis of the database of the departmental Hypertension Clinic of University Hospital of Salerno Medical School, we identified 177 essential hypertensives (age 60.3 ± 13.3 years; 85 men), free from uric acid-modulating medications and severe chronic kidney disease, and whose sUA values, anthropometric, clinical, and echocardiographic data were available. In the studied cohort, the average duration of hypertension was 8.4 ± 7.1 years. LVMi associated with classical determinants, such as age, blood pressure, and kidney function, although after multivariate correction, only age remained significant. Also, sUA correlated positively with LVMi, as well as body size, metabolism, and kidney function. In a multivariate analysis, sUA confirmed the independent association with LVMi. Also, levels of sUA >5.6 mg/dl are associated with larger cardiac size. We confirmed our data in a replicate analysis performed in a larger population (1,379 hypertensives) from an independent clinic. Our results demonstrate that sUA increases with LVMi, and a cutoff of 5.6 mg/dl predict larger LV sizes. Our data suggest that hyperuricemia might help to stratify the risk of larger cardiac size in hypertensives.

Warranty period of normal stress myocardial perfusion imaging in hypertensive patients: A parametric survival analysis.

BACKGROUND: We evaluated the warranty period of a normal stress myocardial perfusion single-photon emission computed tomography (MPS) in hypertensive patients. METHODS AND RESULTS: A total of 471 consecutive hypertensive patients with suspected coronary artery disease and normal perfusion at stress MPS were followed for a mean of 76 ± 21 months. Endpoint events were cardiac death or nonfatal myocardial infarction. With Cox analysis, age (hazard ratio 1.1, P < .005) and stress test type (hazard ratio 2.7, P < .005) were independent predictors of events. With parametric Weibull analysis, patients ≤60 years old undergoing exercise stress test remained at low risk for the entire length of follow-up, while the highest probability of events and the major risk acceleration were observed in those > 60 years old who underwent pharmacologic stress test. In patients undergoing exercise test, peak systolic blood pressure (BP; hazard ratio 1.1, P < .005) emerged as predictor of events, and only subjects with peak systolic BP < 160 mmHg remained at low risk for the entire length of follow-up. In contrast, for patients with peak systolic BP ≥180 mmHg, the time to achieve a cumulative cardiac risk level of 3% was 18 months. CONCLUSIONS: In hypertensive patients, the warranty period of a normal stress MPS varies according to stress type and peak systolic BP. A normal stress MPS can be considered reassuring in subjects ≤60 years old who performed exercise stress test and a peak systolic BP < 160 mmHg.

Cardiopulmonary exercise testing and echocardiographic exam: an useful interaction.

Cardiopulmonary exercise test (CPET) is a functional assessment that helps to detect disorders affecting the system involved in oxygen transport and utilization through the analysis of the gas exchange during exercise. The clinical application of CPET is various, it including training prescription, evaluation of treatment efficacy and outcome prediction in a broad spectrum of conditions. Furthermore, in patients with shortness of breath it provides pivotal information to bring out an accurate differential diagnosis between physical deconditioning, cardiopulmonary disease and muscular diseases. Modern software allows the breath-by-breath analysis of the volume of oxygen intake (VO2), volume of carbon dioxide output (VCO2) and expired air (VE). Through this analysis, CPET provides a series of additional parameters (peak VO2, ventilatory threshold, VE/VCO2 slope, end-tidal carbon dioxide exhaled) that characterize different patterns, helping in diagnosis process. Limitations to the routine use of CPET are mainly represented from the lack of measurement standardization and limited data from randomized multicentric studies. The integration of CPET with exercise stress echocardiography has been recently introduced in the clinical practice by integrating the diagnostic power offered by both the tools. This combined approach has been demonstrated to be valuable for diagnosing several cardiac diseases, including heart failure with preserved or reduced ejection fraction, cardiomyopathies, pulmonary arterial hypertension, valvular heart disease and coronary artery disease. Future investigations are needed to further promote this intriguing combination in the clinical and research setting.

Achievement of target SBP without attention to decrease in DBP can increase cardiovascular morbidity in treated arterial hypertension: the Campania Salute Network.

OBJECTIVES: Results of the SPRINT study have influenced recent guidelines on arterial hypertension, in the identification of target SBP, but scarce attention has been paid to the consequences on DBP. However, there is evidence that reducing DBP too much can be harmful. METHODS: We analyzed outcome in 4005 treated hypertensive patients (22% obesity, 8% diabetes and 21% current smoking habit) with target attended office SBP less than 140 mmHg, in relation to quintiles of DBP, cardiovascular risk profile and target organ damage (LV hypertrophy, carotid plaque and left atrial dilatation). Composite fatal and nonfatal cardiovascular event was the outcome variable in this analysis (stroke and myocardial infarction, sudden cardiac death, heart failure requiring hospitalization, transient ischemic attack, myocardial revascularization, de novo angina, carotid stenting and atrial fibrillation). RESULTS: Lower DBP was associated with greater proportion of women and diabetes, older age, decline in kidney function and greater values of LV mass index and left atrial volume and greater prevalence of carotid plaque (all 0.04 < P < 0.0001). The lowest quintile of DBP (74.1 ±â€Š3.7 mmHg) was associated with 1.49 higher hazard of composite cardiovascular events, independently of significant effect of older age, female sex, LV hypertrophy and borderline effect of left atrial dilatation (0.04 < P < 0.001). CONCLUSION: Increased risk associated with aggressive reduction of DBP should be balanced with the advantage of reducing aggressively SBP to predict the net benefit of antihypertensive treatment, especially in the oldest old individuals.

Coronary vascular function in patients with resistant hypertension and normal myocardial perfusion: a propensity score analysis.

AIMS: Impaired myocardial perfusion reserve (MPR) may occur earlier than coronary atherosclerosis and it may be an early manifestation of developing coronary artery disease (CAD) in patients with resistant hypertension (RH). We evaluated the relationship between RH and MPR in patients with systemic arterial hypertension after balancing for coronary risk factors. METHODS AND RESULTS: We studied 360 subjects without overt CAD and normal myocardial perfusion at stress-rest 82Rb positron emission tomography/computed tomography. To account for differences in baseline characteristics between patients with resistant and controlled hypertension, we created a propensity score-matched cohort considering clinical variables and coronary risk factors. Before matching, patients with RH were significantly older, had higher prevalence of male gender and hypercholesterolaemia, and showed significantly lower global hyperaemic myocardial blood flow (MBF) and MPR compared with those with controlled hypertension, while baseline MBF and coronary artery calcium (CAC) content were similar in both groups. After matching, there were no significant differences in clinical variables and coronary risk factors between patients with resistant and controlled hypertension, but patients with RH still had lower hyperaemic MBF and MPR (both P < 0.001). At univariable and multivariable linear regression analyses, age, RH, and CAC resulted significant predictors of lower MPR values (all P < 0.05). CONCLUSION: After balancing clinical characteristic by propensity score analysis, patients with RH had a blunted hyperaemic MBF and MPR compared with patients with controlled hypertension. The identification of impaired MPR could help to identify early structural alterations of the arterial walls in patients with RH.

Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve.

BACKGROUND: Some components of Nutraceuticals (NUT) such as red yeast rice and Morus alba have demonstrated positive effects on the endothelial function in hypercholesterolemic subjects. Our aim was to compare the effects of two different NUT combinations on cold pressure test (CPT) derived coronary flow reserve (CFR) assessed by transthoracic echo-Doppler. RESULTS: In a randomized, single-blind study, 28 consecutive patients with a variety of cardiovascular risk factors received NUT A (LopiGLIK®: berberine, red yeast rice powder, and leaf extract of Morus alba) or B (Armolipid Plus®: policosanol, red yeast rice, berberine, astaxantine, folic acidandcoenzyme Q10). An echo-Doppler exam with evaluation of CFR was performed at baseline, 2 h (acute test) and 30 days after daily NUT assumption. Blood sampling for metabolic profile and platelet aggregometry was performed at baseline and after 30 days of daily NUT assumption. CFR was not significantly modified at the acute test. After 30 days, CFR improved with NUT A (p < 0.0001), because of the increase of hyperemic flow velocity (p = 0.007), but not with NUT B. CFR was comparable between the two groups at baseline but became significantly higher after 30 days in NUT A (p < 0.02), with a higher CFR percent variation versus baseline (p = 0.008). Total cholesterol and LDL-cholesterol were reduced with both NUT A (p < 0.001 and p < 0.002, respectively) and B (both p < 0.02), whereas platelet aggregation did not significantly change. In the pooled group of patients, after adjusting for age and percent changes of systolic blood pressure, heart rate, LDL-cholesterol and glycemia, NUT A - but not NUT B - was independently associated with CFR changes (ß = 0.599, p = 0.003). CONCLUSIONS: LopiGLIK® improved endothelial-derived CFR, independently of the beneficial effects exerted on the lipid profile. These findings can have clinical reflections on the prevention of age-related inflammatory diseases including coronary artery disease. TRIAL REGISTRATION: (NUTRENDO)″(ClinicalTrials.gov, NCT02969070).

A single blind, multicenter, randomized controlled trial to evaluate the effectiveness and cost of a novel nutraceutical (LopiGLIK®) lowering cardiovascular disease risk.

CONTEXT: Cardiovascular disease (CVD) costs the economy €210 billion per year in Europe. There is an association between low-density lipoprotein cholesterol (LDL-C) and CVD risk. OBJECTIVE: To evaluate the cost and effectiveness of LopiGLIK® (LOPI) in lowering LDL-C and CVD risk. DESIGN: Single blind multicenter randomized controlled trial; patients were divided into two groups, subjected to centralized randomization. SETTING: Four Italian regions. PARTICIPANTS: Thirty-one physicians enrolled 573 adult patients with mild hypercholesterolemia between January 2016 and January 2018. INTERVENTION: Patients were treated for 16 weeks either with LOPI (intervention) or Armolipid Plus® (AP; control). OUTCOME MEASURES: Primary outcome: percentage of patients who achieved LDL-C <130 mg/dL. Secondary outcomes: reduction of HbA1c, survival analysis and HR linked to 38.67 mg/dL reduction of LDL-C and 1% reduction of HbA1c. Costs were assessed per unit and cure. RESULTS: Three hundred and seventy patients treated with LOPI and 203 treated with AP were randomized and completed the study. At baseline 8.9% (n=18) patients treated with AP and 9.5% (n=35) treated with LOPI had LDL-C levels <130 mg/dL (P=0.815). At the 16-week follow-up, 41.4% (n=84) of patients treated with AP and 67.6% (n=250) with LOPI achieved LDL-C levels <130 mg/dL (P<0.001). LOPI patients were three times more likely to achieve LDL-C levels <130 mg/dL; adjusted OR 2.97 (95% CI; 2.08-4.24; P<0.001), number needed to treat was four (95% CI; 5.60-2.90; P<0.001). Survival analysis demonstrated the superiority of LOPI vs AP relative to 38.67 mg/dL LDL-C reduction (P<0.002); HR was 0.761 (95% CI; 0.62-0.94; P<0.001). Both products reduced the HbA1c without a significant difference between them (P=0.156). Survival analysis and HR (0.91; 95% CI; 0.70-1.18) estimated for 1% HbA1c reduction, showed differences between LOPI and AP, which were not significant (P=0.411; P=0.464). The cost of LOPI was €2.11 (unit), €211 (cure), and AP €3.77 and €377, respectively. CONCLUSION: LOPI appeared more effective and less expensive than AP in lowering LDL-C and CVD risk. TRIAL REGISTRATION: NCT02898805, September 8, 2016.

Correction: Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

[This corrects the article DOI: 10.1371/journal.pone.0191172.].

Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

Cardiac eccentric remodeling in patients with rheumatoid arthritis.

It is known that patients with rheumatoid arthritis (RA) have a higher risk of coronary heart disease and sudden cardiac death. Abnormalities in cardiac geometry appear to be involved in the setting of the cardiovascular risk, but it has never been specifically investigated in RA. We enrolled 44 patients with RA compared to 131 subjects without RA (normal, N): The RA aged between 18 and 70 years (mean 48.3 ± 2.1), 25 females, BMI 27.6 ± 0.9; N, of equal age (48.6 ± 1.2, n.s.), included 80 females (BMI 26.7 ± 0.2, ns). Cardiac Ultrasounds showed an increase of the diameter of the left ventricle but not in the septum with reduction of relative wall thickness (RWT) in the RA population compared to N. Relative wall thickness inversely correlates with biochemical parameters of inflammatory response (gamma globulin, p < 0.03; F = 5,660) and anti citrullinated peptides antibody (anti-CCP Ab) (p < 0.02; F = 7,1620) We conclude that unfavorable cardiac remodeling can increase cardiovascular risk in patients with RA.

Effect of a novel nutraceutical combination on serum lipoprotein functional profile and circulating PCSK9.

BACKGROUND: A beneficial effect on cardiovascular risk may be obtained by improving lipid-related serum lipoprotein functions such as high-density lipoproteins (HDLs) cholesterol efflux capacity (CEC) and serum cholesterol loading capacity (CLC) and by reducing proprotein convertase subtilisin kexin type 9 (PCSK9), independently of lipoprotein concentrations. AIM: We aimed to evaluate the effect of an innovative nutraceutical (NUT) combination containing red yeast rice (monacolin K 3.3 mg), berberine 531.25 mg and leaf extract of Morus alba 200 mg (LopiGLIK®), on HDL-CEC, serum CLC and on circulating PCSK9 levels. MATERIALS AND METHODS: Twenty three dyslipidemic subjects were treated for 4 weeks with the above NUT combination. HDL-CEC was measured using specific cell-based radioisotopic assays; serum CLC and PCSK9 concentrations were measured fluorimetrically and by enzyme-linked immunosorbent assay, respectively. RESULTS: The NUT combination significantly reduced plasma level of the total cholesterol and low-density lipoprotein cholesterol (-9.8% and -12.6%, respectively). Despite no changes in HDL-cholesterol, the NUT combination improved total HDL-CEC in 83% of the patients, by an average of 16%, as a consequence of the increase mainly of the ATP-binding cassette A1-mediated CEC (+28.5%). The NUT combination significantly reduced serum CLC (-11.4%) while it did not change PCSK9 plasma levels (312.9±69.4 ng/mL vs 334.8±103.5 mg/L, before and after treatment, respectively). CONCLUSION: The present NUT combination improves the serum lipoprotein functional profile providing complementary beneficial effects, without any detrimental increase of PCSK9 plasma levels.